Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing

ENDNOTES

Prologue

1. Jon Cohen, “What now for human genome editing?,” Science 362, (2018): 1090–1092. http://science.sciencemag.org/content/362/6419/1090.

2. Antonio Regalado, “Exclusive: Chinese scientists are creating CRISPR babies,” MIT Technology Review, November 25, 2018, https://www.technologyreview.com/s/612458/exclusive-chinese-scientists-are-creating-crispr-babies/.

3. Marilynn Marchione, “Chinese researcher claims first gene-edited babies,” Associated Press, November 26, 2018, https://www.apnews.com/4997bb7aa36c45449b488e19ac83e86d.

4. Sui-Lee Wee, “Chinese Scientist Who Genetically Edited Babies Gets 3 Years in Prison,” New York Times December 31, 2019, https://www.nytimes.com/2019/12/30/business/china-scientist-genetic-baby-prison.html.

5. “The era of human gene-editing may have begun. Why that is worrying,” Economist, December 1, 2018, https://www.economist.com/leaders/2018/12/01/the-era-of-human-gene-editing-may-have-begun-why-that-is-worrying.

6. Elizabeth Pennisi, “The CRISPR Craze,” Science 341, (2013): 833–836, https://science.sciencemag.org/content/341/6148/833.

7. “Editing Humanity,” Economist, August 22, 2015, https://www.economist.com/leaders/2015/08/22/editing-humanity.

8. Fraser Nelson, “The return of eugenics,” The Spectator, April 2016, https://www.spectator.co.uk/article/the-return-of-eugenics.

9. Antonio Regalado, “Who Owns the Biggest Biotech Discovery of the Century?,” MIT Technology Review, December 4, 2014, https://www.technologyreview.com/s/532796/who-owns-the-biggest-biotech-discovery-of-the-century/.

10. Amy Maxmen, “The Genesis Engine,” WIRED, August 2015, https://www.wired.com/2015/07/crispr-dna-editing-2/.

11. Kevin Davies, “Nature, genetics and the Niven factor,” Nature Genetics 39, (2007): 805–806, https://www.nature.com/articles/ng0707-805.

12. Kevin Davies and Michael White, Breakthrough: The Race to Find the Breast Cancer Gene (New York: John Wiley & Sons, 1995).

13. Adam Liptak, “Justices, 9–0, Bar Patenting Human Genes,” New York Times, June 13, 2013, https://www.nytimes.com/2013/06/14/us/supreme-court-rules-human-genes-may-not-be-patented.html.

14. Kevin Davies, Cracking the Genome (New York: Free Press, 2001).

15. Kevin Davies, The $1,000 Genome (New York: Free Press, 2010).

16. Fastest genetic diagnosis, Guinness World Records, February 3, 2018, https://www.guinnessworldrecords.com/world-records/413563-fastest-genome-sequencing/.

17. Julianna LeMieux, “MGI Delivers the $100 Genome at AGBT Conference,” Genetic Engineering and Biotechnology News, February 26, 2020, https://www.genengnews.com/news/mgi-delivers-the-100-genome-at-agbt-conference/.

18. Gina Kolata, “Who Needs Hard Drives? Scientists Store Film Clip in DNA,” New York Times, July 12, 2017, https://www.nytimes.com/2017/07/12/science/film-clip-stored-in-dna.html.

19. Y. Shao et al., “Creating a functional single-chromosome yeast,” Nature 560, (2018): 331–335.

20. Matthew Warren, “Four new DNA letters double life’s alphabet,” Nature, February 21, 2019, https://www.nature.com/articles/d41586-019-00650-8.

21. James D. Watson, Andrew Berry, and Kevin Davies, DNA: The Story of the Genetic Revolution (New York: Knopf, 2017).

22. Rob Stein, “In a 1st, Doctors in U.S. Use CRISPR Tool To Treat Patient With Genetic Disorder,” NPR, July 29, 2019, https://www.npr.org/sections/health-shots/2019/07/29/744826505/sickle-cell-patient-reveals-why-she-is-volunteering-for-landmark-gene-editing-st.

23. Michael Specter, “How the DNA Revolution Is Changing Us,” National Geographic, August 2016, https://www.nationalgeographic.com/magazine/2016/08/dna-crispr-gene-editing-science-ethics/.

Chapter 1: The CRISPR Craze

1. Bill Whitaker, “CRISPR: The gene-editing tool revolutionizing biomedical research,” 60 Minutes, April 29, 2018, https://www.cbsnews.com/news/crispr-the-gene-editing-tool-revolutionizing-biomedical-research/.

2. William Kaelin, “Why we can’t cure cancer with a moonshot,” Washington Post, February 11, 2020, https://www.washingtonpost.com/opinions/the-problem-with-trying-to-cure-cancer-with-a-moonshot/2020/02/11/87632bba-2d84-11ea-9b60-817cc18cf173_story.html.

3. Lesley Goldberg, “Jennifer Lopez Sets Futuristic Bio-Terror Drama at NBC (Exclusive),” Hollywood Reporter, October 18, 2016, https://www.hollywoodreporter.com/live-feed/jennifer-lopez-sets-futuristic-bio-939509.

4. Neal Baer, “Covid-19 is scary. Could a rogue scientist use CRISPR to conjure another pandemic?,” STAT, March 26, 2020, https://www.statnews.com/2020/03/26/could-rogue-scientist-use-crispr-create-pandemic/.

5. Walter Isaacson, “Should the rich be allowed to buy the best genes?,” Air Mail, July 27, 2019, https://airmail.news/issues/2019-7-27/should-the-rich-be-allowed-to-buy-the-best-genes.

6. Mary-Claire King, “Emmanuelle Charpentier and Jennifer Doudna: Creators of Gene -Editing Technology,” Time, April 16, 2015, https://time.com/collection-post/3822554/emmanuelle-charpentier-jennifer-doudna-2015-time-100/.

7. Jean-Eric Paquet, Kavli banquet speech, September 4, 2018, http://kavliprize.org/events-and-features/video-2018-kavli-prize-banquet.

8. Leah Sherwood, “Genome editing pioneer and Hilo High graduate Jennifer Doudna speaks at UH Hilo about her discovery: CRISPR technology,” UH Hilo Stories, September 19, 2018, https://hilo.hawaii.edu/news/stories/2018/09/19/genome-editing-pioneer-and-hilo-high-graduate-jennifer-doudna-speaks-at-uh-hilo-about-her-discovery-crispr-technology/.

9. Katie Hasson, “Senate HELP Committee holds hearing on gene editing technology,” Center for Genetics and Society, November 15, 2017, https://www.geneticsandsociety.org/biopolitical-times/senate-help-committee-holds-hearing-gene-editing-technology.

10. U.S. Senate Committee on Health, Education, Labor & Pensions, “Gene Editing Technology: Innovation and Impact,” November 14, 2017, https://www.help.senate.gov/hearings/gene-editing-technology-innovation-and-impact.

11. Pope Francis, “Address of His Holiness Pope Francis to participants at the International Conference organized by the Pontifical Council for Culture on Regenerative Medicine,” April 28, 2018, http://w2.vatican.va/content/francesco/en/speeches/2018/april/documents/papa-francesco_20180428_conferenza-pcc.html.

12. C. Brokowski, “Do CRISPR Germline Ethics Statements Cut It?,” CRISPR Journal 1, (2018): 115–125, https://www.liebertpub.com/doi/10.1089/crispr.2017.0024.

13. April Glaser and Will Oremus, “Tomorrow’s Children, Edited,” Slate, November 28, 2018, https://slate.com/technology/2018/11/if-then-podcast-antonio-regalado-crispr-human-gene-editing-china.html.

14. Francis Collins, “Experts debate: Are we playing with fire when we edit human genes?,” STAT, November 17, 2015, https://www.statnews.com/2015/11/17/gene-editing-embryo-crispr/#Collins.

15. E. S. Lander et al., “Adopt a moratorium on heritable genome editing,” Nature, March 13, 2019, https://www.nature.com/articles/d41586-019-00726-5.

16. Rachel Cocker, “This Harvard scientist wants your DNA to wipe out inherited diseases—should you hand it over?,” Telegraph, March 16, 2019, https://www.telegraph.co.uk/global-health/science-and-disease/harvard-scientist-wants-dna-wipe-inherited-diseases-should/.

17. Sarah Marsh, “Essays Reveal Stephen Hawking Predicted Race of ‘Superhumans’,” Guardian, October 14, 2018, https://www.theguardian.com/science/2018/oct/14/stephen-hawking-predicted-new-race-of-superhumans-essays-reveal.

18. Rob Stein, “First U.S. Patients Treated With CRISPR As Human Gene-Editing Trials Get Underway,” NPR, April 16, 2019, https://www.npr.org/sections/health-shots/2019/04/16/712402435/first-u-s-patients-treated-with-crispr-as-gene-editing-human-trials-get-underway.

Chapter 2: A Cut Above

1. White House, “Announcing the Completion of the First Survey of the Entire Human Genome at the White House,” YouTube video, 40:32, last viewed June 26, 2020, https://www.youtube.com/watch?v=Y_8XRkb-wbY.

2. Nicholas Wade, “Genetic Code of Human Life Is Cracked by Scientists,” New York Times, June 27, 2000, http://movies2.nytimes.com/library/national/science/062700sci-genome.html.

3. Kevin Davies, “Deanna Church on the Reference Genome Past, Present and Future,” Bio-IT World, April 22, 2013, http://www.bio-itworld.com/2013/4/22/church-on-reference-genomes-past-present-future.html.

4. R. Chen and A. J. Butte, “The reference human genome demonstrates high risk of type 1 diabetes and other disorders,” Pacific Symposium on Biocomputing, 2011 (2010): 231–242, https://www.worldscientific.com/doi/abs/10.1142/9789814335058_0025.

5. John Maddox, What Remains To Be Discovered (New York: Free Press, 1999).

6. Fyodor D. Urnov, “Genome Editing B.C. (Before CRISPR): Lessons from the ‘Old Testament,’ ” CRISPR Journal 1, (2018): 115–125, https://www.liebertpub.com/doi/10.1089/crispr.2018.29007.fyu.

7. Shirley Tilghman, in The Gene, PBS, 2020, https://www.pbs.org/kenburns/the-gene/.

8. Rebecca Robbins, “The best and worst analogies for CRISPR, ranked,” STAT, December 8, 2017, https://www.statnews.com/2017/12/08/crispr-analogies-ranked/.

9. Lina Dahlberg and Anna Groat Carmona, “CRISPR-Cas Technology In and Out of the Classroom,” CRISPR Journal 1, (2018): 107–114, https://www.liebertpub.com/doi/10.1089/crispr.2018.0007.

10. C. LaManna and R. Barrangou, “Enabling the Rise of a CRISPR World,” CRISPR Journal 1, (2018): 205–208, https://www.liebertpub.com/doi/10.1089/crispr.2018.0022.

11. K. Davies and R. Barrangou, “MasterChef at Work: An Interview with Rodolphe Barrangou,” CRISPR Journal 1, (2018): 219–222, https://www.liebertpub.com/doi/full/10.1089/crispr.2018.29015.int?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.

12. Hank Greely, quoted in Mark Shwartz, “Target, Delete, Repair,” Stanford Medicine, Winter 2018, https://stanmed.stanford.edu/2018winter/CRISPR-for-gene-editing-is-revolutionary-but-it-comes-with-risks.html.

13. Luciano Marraffini, “CRISPR Frontiers” (discussion, New York Academy of Sciences, February 24, 2020).

14. S. Wiles, “Monday micro—200 million light years of viruses?!,” Infectious Thoughts August 5, 2014, https://sciblogs.co.nz/infectious-thoughts/2014/08/05/monday-micro-200-million-light-years-of-viruses/.

15. S. Klompe and S. H. Sternberg, “Harnessing A Billion Years of Experimentation: The Ongoing Exploration and Exploitation of CRISPR-Cas Immune Systems,” CRISPR Journal 1, (2018): 141-158.

16. Fyodor Urnov in Human Nature (2019), https://wondercollaborative.org/human-nature-documentary-film/.

17. CSHL Leading Strand, “CSHL Keynote, Dr Blake Wiedenheft, Montana State University,” YouTube video, 21:21, last viewed June 26, 2020, https://www.youtube.com/watch?v=2x5VoReHV_4&t=.

18. F. Jiang and J. A. Doudna, “CRISPR-Cas9 Structures and Mechanisms,” Annual Review of Biophysics 46, (2017): 505–529, https://www.annualreviews.org/doi/full/10.1146/annurev-biophys-062215-010822.

19. HHMI BioInteractive, “CRISPR-Cas9 Mechanism & Applications,” https://www.biointeractive.org/classroom-resources/crispr-cas-9-mechanism-applications.

20. M. Shibata et al., “Real-space and real-time dynamics of CRISPR-Cas9 visualized by high-speed atomic force microscopy,” Nature Communications 8, (2017): 1430, https://www.nature.com/articles/s41467-017-01466-8.

21. D. Lawson Jones et al., “Kinetics of dCas9 target search in Escherichia coli,” Science 357, (2017): 1420–1424, https://science.sciencemag.org/content/357/6358/1420?.

22. Andrew Wood, phone interview, August 28, 2019.

23. Rodolphe Barrangou, “CRISPR-Cas: From Bacterial Adaptive Immunity to a Genome Editing Revolution,” XBio, September 2019, https://explorebiology.org/summary/genetics/crispr-cas:-from-bacterial-adaptive-immunity-to-a-genome-editing-revolution

24. S. Hwang and K. L. Maxwell, “Meet the Anti-CRISPRs: Widespread Protein Inhibitors of CRISPR-Cas Systems,” CRISPR Journal 2, (2019): 23–30, https://www.liebertpub.com/doi/full/10.1089/crispr.2018.0052.

25. M. Adli, “The CRISPR tool kit for genome editing and beyond.” Nature Communications 9, (2018): 1911, https://www.nature.com/articles/s41467-018-04252-2.

26. P. T. Harrison and S. Hart, “A beginner’s guide to gene editing,” Experimental Physiology 103, (2018): 439–448, https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/EP086047.

27. Jennifer Doudna, Keystone Symposium, Banff, Canada, February 9, 2020.

Chapter 3: We Can Be Heroes

1. Fyodor Urnov, “Genome Engineering,” Keystone Symposium, Victoria Island, Canada, February 21, 2019.

2. Francisco Mojica, interview, Santa Pola, Spain, May 1, 2018.

3. Ed Yong, “The Unique Merger That Made You (and Ewe, and Yew),” Nautilus, February 6, 2014, http://nautil.us/issue/10/mergers--acquisitions/the-unique-merger-that-made-you-and-ewe-and-yew.

4. Manuel Ansede, “Francis Mojica, de las salinas a la quiniela del Nobel,” El País, May 18, 2017, https://elpais.com/elpais/2017/05/18/eps/1495058731_149505.html.

5. F. J. M. Mojica et al., Transcription at different salinities of Haloferax mediterranei sequences adjacent to partially modified PstI sites. Molecular Microbiology 9, (1993): 613–621.

6. Y. Ishino et al., “Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product,” Journal of Bacteriology 169, (1987): 5429–5433, https://jb.asm.org/content/jb/169/12/5429.full.pdf.

7. F. J. M. Mojica et al., “Long stretches of short tandem repeats are present in the largest replicons of the Archaea Haloferax mediterranei and Haloferax volcanii and could be involved in replicon partitioning,” Molecular Microbiology 17, (1995): 85–93, DOI: 10.1111/j.1365 -2958.1995.mmi_17010085.x.

8. Clara Rodriguez Fernandez, “Interview with Francis Mojica, the Spanish scientist that [sic] discovered CRISPR,” Labiotech, November 13, 2017, https://labiotech.eu/francis-mojica-crispr-interview/.

9. B. Masepohl et al., “Long tandemly repeated repetitive (LTRR) sequences in the filamentous cyanobacterium Anabaena sp. PCC 7120,” Biochimica et Biophysica Acta 1307, (1996): 26–30, https://www.sciencedirect.com/science/article/abs/pii/0167478196000401.

10. K. S. Makarova et al., “A DNA repair system specific for thermophilic Archaea and bacteria predicted by genomic context analysis,” Nucleic Acids Research 30, (2002): 482–496, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC99818/.

11. K. Davies and F. Mojica, “Crazy About CRISPR: An Interview with Francisco Mojica,” CRISPR Journal 1, (2018): 29–33, https://www.liebertpub.com/doi/10.1089/crispr.2017.28999.int.

12. Ibid.

13. Molly Campbell, “Francisco Mojica: The Modest Microbiologist Who Discovered and Named CRISPR,” Technology Networks, October 14, 2019, https://www.technologynetworks.com/genomics/articles/francis-mojica-the-modest-microbiologist-who-discovered-and-named-crispr-325093.

14. K. Davies and F. Mojica, “Crazy About CRISPR: An Interview with Francisco Mojica,” CRISPR Journal 1, (2018): 29–33, https://www.liebertpub.com/doi/10.1089/crispr.2017.28999.int.

15. César Díez-Villaseñor, email, October 28, 2017.

16. F. J. M. Mojica et al., “Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive From Foreign Genetic Elements,” Journal of Molecular Evolution 60, (2005): 174–182, https://link.springer.com/article/10.1007%2Fs00239-004-0046-3.

17. F. J. M. Mojica and F. Rodriguez-Valera, “The discovery of CRISPR in archaea and bacteria,” FEBS Journal 283, (2016): 3162–3169, https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.13766.

18. C. Pourcel et al., “CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies,” Microbiology 151, (2005): 653–663, https://mic.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.27437-0.

19. A. Bolotin et al., “Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin,” Microbiology 151, (2005): 2551–2661.

20. Philippe Horvath, interview, Vilnius, Lithuania, June 21, 2018.

21. K. Davies and R. Barrangou, “MasterChef at Work: An Interview with Rodolphe Barrangou,” CRISPR Journal 1, 219–222 (2018), https://www.liebertpub.com/doi/10.1089/crispr.2018.29015.int.

22. K. Davies and S. Moineau, “The Phage Whisperer: An Interview with Sylvain Moineau,” CRISPR Journal 1, (2018): 363–366, https://www.liebertpub.com/doi/10.1089/crispr.2018.29037.kda.

23. R. Barrangou et al., “CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes,” Science 315, (2007): 1709-1712, DOI: 10.1126/science.1138140.

24. Philippe Horvath, “New Hot Papers—2008,” Science Watch, July 2008, http://archive.sciencewatch.com/dr/nhp/2008/pdf/08julnhpHorvath.pdf.

Chapter 4: “Thelma and Louise”

1. Jennifer Kahn, “The CRISPR Quandary,” New York Times Magazine, November 9, 2015, https://www.nytimes.com/2015/11/15/magazine/the-crispr-quandary.html.

2. Colin Tudge, The Engineer in the Garden (New York: Hill and Wang, 1994).

3. Melissa Marino, “Biography of Jennifer A. Doudna,” Proceedings of the National Academy of Sciences 101, (2004): 16987–16989, https://www.pnas.org/content/101/49/16987.

4. Vic Myer, Keystone symposium, Banff, Canada, February 9, 2020.

5. K. Makarova et al., “A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action,” Biology Direct 1, (2006): 7, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1462988/.

6. Jennifer Doudna, “Jennifer Doudna on the future of gene editing,” Berkeley News, April 10, 2019, https://news.berkeley.edu/2019/04/10/berkeley-talks-transcript-jennifer-doudna-future-of-gene-editing/.

7. K. D. Seed et al., “A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity,” Nature 494, (2013): 489–491, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587790/.

8. B. Al-Shayeb et al., “Clades of huge phages from across Earth’s ecosystems,” Nature 578, (2013): 425–431, https://www.nature.com/articles/s41586-020-2007-4.

9. Jill Banfield, in Human Nature, 2019, https://wondercollaborative.org/human-nature-documentary-film/.

10. Ross Wilson, interview, San Francisco, March 13, 2019.

11. B. Wiedenheft et al., “Structural basis for DNase activity of a conserved protein implicated in CRISPR-mediated genome defense,” Structure 17, (2009): 904–912, https://doi.org/10.1016/j.str.2009.03.019.

12. Lisa Jarvis, “A day in the life of Jennifer Doudna,” Chemical & Engineering News, March 8, 2020, https://cen.acs.org/biological-chemistry/gene-editing/A-day-with-Jennifer-Doudna-Trying-to-keep-up-with-one-of-the-world-most-sought-after-scientists/98/i9.

13. Press release, “Genentech announces vice president appointment in research,” January 21, 2009, https://www.gene.com/media/press-releases/11787/2009-01-21/genentech-announces-vice-president-appoi.

14. M. Jínek and J. A. Doudna, “A three-dimensional view of the molecular machinery of RNA interference,” Nature 457, (2009): 405–412, https://www.nature.com/articles/nature07755.

15. Katrin Koller, “You should always have something crazy cooking on the back burner,” BaseLaunch, October 17, 2017, https://www.baselaunch.ch/you-should-always-have-something-–crazy-cooking-on-the-back-burner-2/.

16. H. Deveau et al., “Phage Response to CRISPR-Encoded Resistance in Streptococcus thermophilus,” Journal of Bacteriology 190, (2008): 1390–1400, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2238228/.

17. F. J. M. Mojica et al., “Short Motif Sequences Determine the Targets of the Prokaryotic CRISPR Defence System,” Microbiology 155, (2009): 733740.

18. A. F. Andersson and J. F. Banfield, “Virus Population Dynamics and Acquired Virus Resistance in Natural Microbial Communities,” Science 320, (2008): 1047–1050, https://science.sciencemag.org/content/320/5879/1047.abstract.

19. S. J. J. Brouns et al., “Small CRISPR RNAs guide antiviral defense in prokaryotes,” Science 321, (2008): 960–964, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898235/.

20. Mark van der Meijs, “ ‘Without John van der Oost, CRISPR-Cas would never have become this big,’ ” Resource, June 19, 2019, https://resource.wur.nl/en/science/show/Without-John-van-der-Oost-CRISPR-Cas-would-never-have-become-this-big-.htm.

21. L. A. Marraffini and E. J. Sontheimer, “CRISPR interference limits horizontal gene transfer in Staphylococci by targeting DNA,” Science 322, (2008): 1843–1845, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695655/.

22. Will Doss, “The CRISPR Revolution,” Northwestern Medicine, February 16, 2018, https://magazine.nm.org/2018/02/16/the-crispr-revolution/.

23. K. Davies and S. Moineau, “The Phage Whisperer: An Interview with Sylvain Moineau,” CRISPR Journal 1, (2018): 363–366, https://www.liebertpub.com/doi/10.1089/crispr.2018.29037.kda.

24. J. E. Garneau et al., “The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA,” Nature 468, (2010): 67–71, https://www.nature.com/articles/nature09523.

25. Pauline Freour, “Emmanuelle Charpentier: ‘Des qu’on manipule le vivant, il y a un risqué de derive,’ ” Le Figaro, March 22, 2016, http://sante.lefigaro.fr/actualite/2016/03/22/24766-emmanuelle-charpentier-quon-manipule-vivant-il-y-risque-derive.

26. Alison Abbott, “The quiet revolutionary: How the co-discovery of CRISPR explosively changed Emmanuelle Charpentier’s life,” Nature, April 27, 2016, https://www.nature.com/news/the-quiet-revolutionary-how-the-co-discovery-of-crispr-explosively-changed-emmanuelle-charpentier-s-life-1.19814.

27. Florence Rosier, “Emmanuelle Charpentier, le ‘charmant petit monstre’ du génie génétique,” Le Monde, January 9, 2015, https://www.lemonde.fr/sciences/article/2018/05/31/emmanuelle-charpentier-le-charmant-petit-monstre-du-genie-genetique_4559167_1650684.html.

28. N. Herzberg, “Les nouvelles icones de la biologie,” Le Monde, August 1, 2018, https://www.lemonde.fr/festival/article/2016/08/01/la-piste-aux-etoiles_4977125_4415198.html.

29. The annual lecture is given in honor of the son of Columbia University chemistry professor Stephen Lippard, who died age seven of a neurological disease. Emmanuelle Charpentier, “The 44th Annual Andrew Mark Lippard Memorial Lecture,” (lecture, Columbia University, New York, September 26, 2018), http://www.columbianeurology.org/44th-annual-andrew-mark-lippard-memorial-lecture.

30. Jacques Monod, Chance and Necessity (New York: Vintage Books, 1972).

31. E. Charpentier, “The Kavli Prize: An autobiography by: Emmanuelle Charpentier,” 2018, http://kavliprize.org/sites/default/files/%25nid%25/autobiagraphies_attachments/Emmanuelle%20Charpentier_autobiography.pdf.

32. K. Davies and E. Charpentier, “Finding Her Niche: An Interview with Emmanuelle Charpentier,” CRISPR Journal 2, (2019):17–22, https://www.liebertpub.com/doi/10.1089/crispr.2019.29042.kda

33. Ibid.

Chapter 5: DNA Surgery

1. E. Deltcheva et al., “CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III,” Nature 471, (2011): 602–607, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070239/.

2. Jennifer Kahn, “The Crispr Quandary,” New York Times Magazine, November 9, 2015, https://www.nytimes.com/2015/11/15/magazine/the-crispr-quandary.html.

3. K. Davies and M. Jínek, “The CRISPR-RNA World: An Interview with Martin Jínek,” CRISPR Journal 3, (2020): 68–72, https://www.liebertpub.com/doi/10.1089/crispr.2020.29091.mji.

4. Jennifer Doudna, “Why genome editing will change our lives,” Financial Times, March 14, 2018, https://www.ft.com/content/582d382c-2647-11e8-b27e-cc62a39d57a0.

5. M. Jínek et al., “A programmable dual-RNA—guided DNA endonuclease in adaptive bacterial immunity,” Science 337, (2012): 816–821, https://science.sciencemag.org/content/337/6096/816/tab-article-info.

6. DOE/Lawrence Berkeley National Laboratory, “Programmable DNA scissors found for bacterial immune system,” Science Daily, June 28, 2012, https://www.sciencedaily.com/releases/2012/06/120628193020.htm.

7. A. Pollack, “A powerful new way to edit DNA,” New York Times, March 3, 2014, https://www.nytimes.com/2014/03/04/health/a-powerful-new-way-to-edit-dna.html.

8. S. M. Lee, “Editing DNA could be genetic medicine breakthrough,” San Francisco Chronicle, September 7, 2014, https://www.sfchronicle.com/technology/article/Editing-DNA-could-be-genetic-medicine-breakthrough-5740320.php.

9. S. J. J. Brouns, “A Swiss Army Knife of Immunity,” Science 337, (2012): 808–809, https://science.sciencemag.org/content/337/6096/808.

10. Fyodor Urnov in Human Nature (2019), https://wondercollaborative.org/human-nature-documentary-film/.

11. R. Barrangou, “RNA-mediated programmable DNA cleavage,” Nature Biotechnology 30, (2012): 836–868, https://www.nature.com/articles/nbt.2357.

12. Rodolphe Barrangou, interview, Victoria, Canada, February 21, 2019.

13. D. Carroll, “A CRISPR Approach to Gene Targeting,” Molecular Therapy 20, (2012): 1656–1660, https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)32156-6.

14. R. Sapranauskas et al., “The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli,” Nucleic Acids Research 39, (2011): 9275–9282, doi.org/10.1093/nar/gkr606.

15. “Cool,” vol. 1, number 1, July 30, 1990, http://cell.com/pb/assets/raw/journals/research/cell/cell-timeline-40/spoof.pdf.

16. K. Davies and V. Siksnys, “From Restriction Enzymes to CRISPR: An Interview with Virginijus Siksnys,” CRISPR Journal 1, (2018): 137–140, https://www.liebertpub.com/doi/10.1089/crispr.2018.29008.vis.

17. G. Gasiunas et al., “Cas9–crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria,” Proceedings of the National Academy of Sciences 109, (2012): E2579–E2586, https://www.pnas.org/content/109/39/E2579?iss=39.

18. Sarah Zhang, “The Battle Over Genome Editing Gets Science All Wrong,” WIRED, April 18, 2015, https://www.wired.com/2015/10/battle-genome-editing-gets-science-wrong/.

19. R. Dahm, “Friedrich Miescher and the Discovery of DNA,” Developmental Biology 278, (2005); 274–288, https://doi.org/10.1016/j.ydbio.2004.11.028.

20. Stuart Firestein, “Fundamentally Newsworthy,” The Edge.org, 2016, “Youtube, https://www.edge.org/response-detail/26718.

21. TEDx Talks, “O(ú)pravy lidské DNA | Martin Jínek | TEDx Třinec,” YouTube video, 21:07, last viewed June 26, 2020, https://www.youtube.com/watch?v=d7kPcjD3PUU.

22. Jin-Soo Kim, email to Doudna and Charpentier, October 3, 2012. PTAB Interference 106048. UC exhibit 1558, https://acts.uspto.gov/ifiling/PublicView.jsp?identifier=106048.

23. George Church, email to Doudna, November 14, 2012. PTAB Interference 106048. UC exhibit 1559, https://acts.uspto.gov/ifiling/PublicView.jsp?identifier=106048.

24. Lisa Jarvis, “A day in the life of Jennifer Doudna,” Chemical & Engineering News, March 8, 2020, https://cen.acs.org/biological-chemistry/gene-editing/A-day-with-Jennifer-Doudna-Trying-to-keep-up-with-one-of-the-world-most-sought-after-scientists/98/i9.

25. M. Jínek et al., “RNA programmed genome editing in human cells,” eLife 2, (2013): e00471. https://elifesciences.org/articles/00471.

26. Feng Zhang, email to Doudna, January 2, 2013, PTAB Interference 106048, UC exhibit 1620, https://acts.uspto.gov/ifiling/PublicView.jsp?identifier=106048.

Chapter 6: Field of Dreams

1. M. Boguski, “A Molecular Biologist Visits Jurassic Park,” BioTechniques 12, (1992): 668–669, http://markboguski.net/docs/publications/BioTechniques-1992.pdf.

2. Alice Park, “The editor of life’s building blocks,” Time, October 6, 2016, https://time.com/4518815/feng-zhang-next-generation-leaders/.

3. Carey Goldberg, “CRISPR Wizard Feng Zhang: The Making Of A Sunny Science Superstar,” WBUR, April 26, 2018, https://www.wbur.org/commonhealth/2018/04/26/feng-zhang-crispr-profile.

4. Ingfei Chen, “The beam of light that flips a switch that turns on the brain,” New York Times, August 14, 2007, https://www.nytimes.com/2007/08/14/science/14brai.html.

5. John Colapinto, “Lighting the Brain,” New Yorker, May 18, 2015, https://www.newyorker.com/magazine/2015/05/18/lighting-the-brain.

6. Kerry Grens, “Feng Zhang: The Midas of Methods,” The Scientist, August 1, 2014, https://www.the-scientist.com/?articles.view/articleNo/40582/title/Feng-Zhang--The-Midas-of-Methods/.

7. F. Zhang, L. Cong et al., “Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription,” Nature Biotechnology 29, (2011): 149–153, https://www.nature.com/articles/nbt.1775.

8. Le Cong, phone interview, July 18, 2019.

9. Michael Gilmore, email, July 7, 2019.

10. K. L. Palmer and M. S. Gilmore, “Multidrug-resistant enterococci lack CRISPR-cas,” mBio (2010): 1:e00227–10, https://mbio.asm.org/content/1/4/e00227-10/article-info.

11. P. Horvath and R. Barrangou, “CRISPR/Cas, the Immune System of Bacteria and Archaea,” Science 327, (2010): 167–170, https://science.sciencemag.org/content/327/5962/167.long.

12. J. E. Garneau et al., “The CRISPR/Cas Bacterial Immune System Cleaves Bacteriophage and Plasmid DNA,” Nature 468, (2010): 67–71, https://www.nature.com/articles/nature09523.

13. Broad Institute, https://www.broadinstitute.org/files/news/pdfs/BroadPriorityStatement.pdf.

14. MIT McGovern Institute, “Meet Feng Zhang,” YouTube video, 4:12, last viewed January 3, 2020, https://www.youtube.com/watch?v=EjolOzkYNlk&t=.

15. Luciana Marraffini, personal communication, September 23, 2019.

16. D. Altshuler and D. Cowan, “Isogenic Human Pluripotent Stem Cell-Based Models of Human Disease Mutations,” Grant ID: R01-DK-097768, https://commonfund.nih.gov/TRA/recipients12.

17. Sharon Begley, “Meet one of the world’s most groundbreaking scientists. He’s 34.” STAT, November 6, 2015, https://www.statnews.com/2015/11/06/hollywood-inspired-scientist-rewrite-code-life/.

18. Amy Maxmen, “Easy DNA editing will remake the world. Buckle up,” WIRED, December 2015, https://www.wired.com/2015/07/crispr-dna-editing-2/.

19. Le Cong, phone interview, July 18, 2019.

20. Fei Ann Ran, interview, Boston, August 2, 2019.

21. TEDx Talks, “Inspired by nature: harnessing tools from microbes to engineer biology | Fei Ann Ran | TEDxVienna,” YouTube video, 15:55, last viewed November 10, 2019, https://www.youtube.com/watch?v=dcD0G1-BPGE.

22. Fei Ann Ran, interview, Boston, August 2, 2019.

23. George Church, interview, Boston, August 2, 2019.

24. K. Davies and K. Esvelt, “Gene Drives, White-Footed Mice, and Black Sheep: An Interview with Kevin Esvelt,” CRISPR Journal 1, (2018): 319–324, https://www.liebertpub.com/doi/10.1089/crispr.2018.29031.kda.

25. Rodolphe Barrangou, interview, Victoria, Canada, February 21, 2019.

26. L. Cong, F. A. Ran et al., “Multiplex genome engineering using CRISPR/Cas systems,” Science 339, (2013): 819–823, http://science.sciencemag.org/content/339/6121/819.full.

27. P. Mali et al., “RNA-guided human genome engineering via Cas9,” Science 339, (2013): 823–826, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712628/.

28. S. W. Cho et al., “Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease,” Nature Biotechnology 31, (2013): 230–232, https://www.nature.com/articles/nbt.2507.

29. W. Y. Hwang et al., “Efficient genome editing in zebrafish using a CRISPR-Cas system,” Nature Biotechnology 31, (2013): 277–279, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686313/.

30. W. Jiang et al., “CRISPR-assisted editing of bacterial genomes,” Nature Biotechnology 31, (2013): 233–239, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748948/.

31. Hannah Devlin, “Jennifer Doudna: ‘I have to be true to who I am as a scientist,’ ” Guardian, July 2, 2017, https://www.theguardian.com/science/2017/jul/02/jennifer-doudna-crispr-i-have-to-be-true-to-who-i-am-as-a-scientist-interview-crack-in-creation.

32. Matt Ridley, “Editing Our Genes, One Letter at a Time,” Wall Street Journal, January 11, 2013, https://www.wsj.com/articles/SB10001424127887323482504578227661405130902.

33. Matthew Herper, “This protein could change biotech forever,” Forbes, March 19, 2013, https://www.forbes.com/sites/matthewherper/2013/03/19/the-protein-that-could-change-biotech-forever/.

34. K. Karczewski, “Progress in genomics according to bingo: 2013 edition,” Genome Biology 14, (2013): 143, https://genomebiology.biomedcentral.com/articles/10.1186/gb4148.

35. Q. Ding et al., “Enhanced Efficiency of Human Pluripotent Stem Cell Genome Editing through Replacing TALENs with CRISPRs,” Cell Stem Cell 12, (2013): 393–394, https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(13)00101-X

36. T. J. Cradick, online interview, June 30, 2020.

37. Jon Cohen, “The Birth of CRISPR Inc.,” Science 355, (2017): 680–684, https://science.sciencemag.org/content/355/6326/680.summary.

38. R. Coontz, “Science’s top ten breakthroughs of 2013,” Science, December 19, 2013, https://www.sciencemag.org/news/2013/12/sciences-top-10-breakthroughs-2013.

39. John Travis, “Breakthrough of the Year: CRISPR makes the cut,” Science, December 17, 2015, https://www.sciencemag.org/news/2015/12/and-science-s-2015-breakthrough-year.

Chapter 7: Prize Fight

1. Patrick Gillooly, “Lander named to Obama’s science team,” MIT News, December 22, 2008, http://news.mit.edu/2008/lander-named-obamas-science-team.

2. Veronique Greenwood and Valerie Ross, “How Feng Zhang modified a cell’s genome on the fly,” Popular Science, October 23, 2013, https://www.popsci.com/science/article/2013-09/feng-zhang/.

3. Eric S. Lander, “The heroes of CRISPR,” Cell 164, (2016): 18–28, https://www.cell.com/cell/pdf/S0092-8674(15)01705-5.pdf.

4. Michael Eisen, “The villain of CRISPR,” It is NOT Junk (blog), January 25, 2016, http://www.michaeleisen.org/blog/?p=1825.

5. Nathaniel Comfort, “A Whig history of CRISPR,” Genotopia, January 18, 2016, https://genotopia.scienceblog.com/573/a-whig-history-of-crispr/.

6. Jennifer Doudna, “PubMed Commons,” 2016, posted by Richard Sever, https://twitter.com/search?q=pubmed%20commons%20charpentier&src=typd.

7. Bob Grant, “Credit for CRISPR: A Conversation with George Church,” The Scientist, December 29, 2015, https://www.the-scientist.com/news-analysis/credit-for-crispr-a-conversation-with-george-church-34306.

8. George Church, interview, Boston, August 2, 2019.

9. Samuel Sternberg, “Humans By Design: Covering the Genome Editing Revolution,” New York University, March 6, 2018, https://journalism.nyu.edu/about-us/event/2018-spring/humans-by-design-covering-the-gene-editing-revolution/.

10. Jennifer A. Doudna and Samuel H. Sternberg, A Crack in Creation (Boston: Houghton Mifflin Harcourt, 2017).

11. CanadaGairdnerAwards, “Jennifer Doudna-2016 Canada Gairdner Awards Gala,” YouTube video, 5:31, last viewed May 1, 2020, https://www.youtube.com/watch?v=jLOSMcQ2iec&t=.

12. Rodolphe Barrangou, interview, Victoria, Canada, February 21, 2019.

13. Ibid.

14. Albany Med, “Albany Medical Center Prize in Medicine and Biomedical Research panel discussion,” YouTube video, 1:23:27, last viewed May 10, 2020, https://www.youtube.com/watch?v=oNlukM56bsY.

15. Clara Rodriguez Fernandez, “Francis Mojica, the Spanish Scientist Who Discovered CRISPR,” Labiotech, April 8, 2019, https://labiotech.eu/interviews/francis-mojica-crispr-interview/.

16. Jennifer A. Doudna, “The promise and challenge of therapeutic genome editing,” Nature 578, (2020): 229–236, https://www.nature.com/articles/s41586-020-1978-5?proof=true.

17. L. S. Qi et al., “Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression,” Cell 152, (2013): 1173–1184, https://www.cell.com/fulltext/S0092-8674(13)00211-0.

18. H. A. Rees and D. R. Liu, “Base editing: Precision Chemistry on the Genome and Transcriptome of Living Cells,” Nature Reviews Genetics 19, (2018): 770–788, https://pubmed.ncbi.nlm.nih.gov/30323312/.

19. B. L. Oakes et al., “CRISPR-Cas9 Circular Permutants as Programmable Scaffolds for Genome Modification,” Cell 176, (2019): 254–267, https://pubmed.ncbi.nlm.nih.gov/30633905/.

20. D. Burstein et al., “New CRISPR–Cas systems from uncultivated microbes,” Nature 542, 2017: 237–241.

21. B. Zetsche et al., “Cpf1 Is a Single RNA-guided Endonuclease of a Class 2 CRISPR-Cas System,” Cell 163, (2015): 759–771, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638220/.

22. J. S. Chen et al., “CRISPR-Cas12a target binding unleashes indiscriminate single-strand DNase activity,” Science 360, (2018): 436–439, https://science.sciencemag.org/content/360/6387/436.

23. J. P. Broughton et al., “CRISPR-Cas12-based detection of SARS-CoV-2,” Nature Biotechnology, 2020, https://www.nature.com/articles/s41587-020-0513-4.

24. J. S. Gootenberg et al., “Nucleic acid detection with CRISPR-Cas13a/C2c2,” Science 356, (2017): 438–442, https://science.sciencemag.org/content/356/6336/438.

25. John Carreyrou, Bad Blood (New York: Knopf, 2018).

26. M. B. Nourse et al., “Engineering of a miniaturized, robotic clinical laboratory,” Bioeng. Transl. Med. 3, 58–70 (2018), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773944/.

27. O. O. Abudayyeh et al., “Nucleic acid detection of plant genes using CRISPR-Cas13,” CRISPR Journal 2, (2019): 165-171, https://www.liebertpub.com/doi/10.1089/CRISPR.2019.0011.

28. Elie Dolgin, “The kill-switch for CRISPR that could make gene-editing safer,” Nature January 15, 2020, https://www.nature.com/articles/d41586-020-00053-0.

29. S. E. Klompe et al., “Transposon-encoded CRISPR–Cas systems direct RNA-guided DNAintegration,” Nature 571, (2019): 219–225, https://www.nature.com/articles/s41586-019-1323-z.

Chapter 8: Genome Editing B.C.

1. Fyodor Urnov, TRI-CON, San Francisco, February 15, 2018.

2. Editorial, “Method of the Year 2011,” Nature Methods 9, (2012): 1, https://doi.org/10.1038/nmeth.1852.

3. Mario R. Cappechi, “The making of a scientist,” HHMI Bulletin, May 1997, https://healthcare.utah.edu/capecchi/HHMI.pdf.

4. Ibid.

5. F. D. Urnov, “Genome Editing B.C. (Before CRISPR): Lasting Lessons from the ‘Old Testament,’ ” CRISPR Journal 1, (2018): 34–46, https://www.liebertpub.com/doi/10.1089/crispr.2018.29007.fyu.

6. Fyodor Urnov, interview, Florence, Italy, June 27, 2018.

7. http://sangamoncountyhistory.org/wp/?p=1410.

8. Ed Lanphier, interview, Ross, California, March 4, 2019.

9. S. Hacein-Bey-Abina et al., “Sustained Correction of X-Linked Severe Combined Immunodeficiency by Ex Vivo Gene Therapy,” New England Journal of Medicine 346, (2002): 1185–1193, https://www.nejm.org/doi/full/10.1056/NEJMoa012616.

10. Douglas Birch, “Hamilton Smith’s second chance; Scientist’s journey; He won the Nobel, but lost his way. Could he put his family together? And could he crack one of life’s great puzzles?,” Baltimore Sun, April 11, 1999, https://www.baltimoresun.com/news/bs-xpm-1999-04-11-9904120283-story.html.

11. Ibid.

12. Y. G. Kim, J. Cha, and S. Chandrasegaran, “Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain,” Proceedings of the National Academy of Sciences USA 93, (1996): 1156–1160, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40048/.

13. S. Chandrasegaran and J. Smith, “Chimeric Restriction Enzymes: What is Next?,” Biological Chemistry 380, (1999): 841–848, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033837/.

14. M. Bibikova et al., “Targeted Chromosomal Cleavage and Mutagenesis in Drosophila Using Zinc-Finger Nucleases,” Genetics 161, (2002): 1169–1175, https://www.genetics.org/content/161/3/1169.long.

15. M. Bibikova et al., “Stimulation of Homologous Recombination through Targeted Cleavage by Chimeric Nucleases,” Molecular and Cellular Biology 21, (2001): 289–297, https://mcb.asm.org/content/21/1/289.

16. K. Davies and D. Carroll, “Giving Genome Editing the Fingers: An Interview with Dana Carroll,” CRISPR Journal 2, (2019): 157–162, https://www.liebertpub.com/doi/10.1089/crispr.2019.29058.dca.

17. M. H. Porteus and D. Baltimore, “Chimeric nucleases stimulate gene targeting in human cells,” Science 5620, (2003): 763, http://science.sciencemag.org/content/300/5620/763.

18. F. D. Urnov et al., “Highly Efficient Endogenous Human Gene Correction Using Designed Zinc-Finger Nucleases,” Nature 435, (2005): 646–651, https://www.nature.com/articles/nature03556.

19. S. Jaffe, “Giving Genetic Disease the Finger,” WIRED, July 5, 2005, https://www.wired.com/2005/07/giving-genetic-disease-the-finger/.

20. K. Kandavelou et al., “ ‘Magic’ scissors for genome surgery,” Nature Biotechnology 23, (2005): 686–687, https://www.nature.com/articles/nbt0605-686.

21. B. J. Doranz et al., “A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors,” Cell 85, (1996): 1148–58, https://www.cell.com/cell/fulltext/S0092-8674(00)81314-8.

22. M. Parmentier, “CCR5 an HIV infection, a view from Brussels,” Frontiers in Immunology 6, (2015): 295, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459230/.

23. M. Samson et al., “Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene,” Nature 382, (1996): 722–725, https://www.nature.com/articles/382722a0.

24. Stephen J. O’Brien, Tears of the Cheetah (New York: Thomas Dunne, 2003).

25. T. R. Brown, “I am the Berlin patient: a personal reflection,” AIDS Research and Human Retroviruses 31, (2015): 2–3, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287108/.

26. G. Hutter et al., “Long-term control of HIV by CCR5 delta32/delta32 stem-cell transplantation,” New England Journal of Medicine 360, (2009): 692–698, https://www.nejm.org/doi/full/10.1056/NEJMoa0802905.

27. F. Urnov, “AWESOME interview with Dr. Fyodor Urnov,” The Sangamo Domain (blog), December 12, 2015, http://sangamodomain.blogspot.com/2015/12/awesome-interview-with-dr-fyodor-urnov.html.

28. P. Tebas et al., “Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV,” New England Journal of Medicine 370, (2014): 901–910, https://www.nejm.org/doi/full/10.1056/nejmoa1300662.

29. Emily Mullin, “Back to the Future: Pre-CRISPR Systems are Driving Therapies to the Clinic,” Genetic Engineering & Biotechnology News, February 7, 2019, https://www.genengnews.com/insights/back-to-the-future-pre-crispr-systems-are-driving-therapies-to-the-clinic/.

30. CNBC, “Sangamo Biosciences CEO Edward Lanphier | Mad Money | CNBC,” YouTube video, 8:19, March 7, 2019, https://www.youtube.com/watch?v=c3dT1sH1PNM.

31. Brian Madeux quoted in M. Marchione, “US scientists try 1st gene editing in the body,” AP News, November 15, 2017, https://apnews.com/4ae98919b52e43d8a8960e0e260feb0a.

32. C. Hunter, “A rare disease in two brothers,” Journal of the Royal Society of Medicine 10, (1917): 104–116, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2018097/pdf/procrsmed00727-0110.pdf.

33. Sandy Macrae, Genome Editing summit, National Academy of Sciences, Washington, DC, August 13, 2019, https://vimeo.com/showcase/6229550/video/354892447.

34. B. Zeitler et al., “Allele-specific transcriptional repression of mutant HTT for the treatment of Huntington’s disease,” Nature Medicine 25, (2019): 1131–1142, https://www.nature.com/articles/s41591-019-0478-3.

35. Ed Rebar, “Genome Engineering,” (lecture, Keystone Symposium, Victoria, Canada, February 2019).

Chapter 9: Deliverance or Disaster

1. Anon, “Mount Hope geneticists get more milk from cows by selective breeding,” Life 5, 50–53 (1938).

2. J. A. Wolff and J. Lederberg, “An early history of gene transfer and therapy,” Human Gene Therapy 5, (1994): 469–480, https://www.liebertpub.com/doi/abs/10.1089/hum.1994.5.4-469.

3. Derek So, “The Use and Misuse of Brave New World in the CRISPR Debate,” CRISPR Journal 2, (2019): 316–323, https://www.liebertpub.com/doi/10.1089/crispr.2019.0046.

4. Jack Williamson, Dragon’s Island (New York: Simon & Schuster, 1951).

5. Francis Crick, letter to Michael Crick, March 15, 1953, Wellcome Library, https://wellcomelibrary.org/item/b1948799x.

6. J. D. Watson, correspondence: Letter to Max Delbruck, March 12, 1953, http://scarc.library.oregonstate.edu/coll/pauling/dna/corr/corr432.1-watson-delbruck-19530312-transcript.html.

7. Brenda Maddox, “DNA’s double helix: 60 years since life’s deep molecular secret was discovered,” Guardian, February 22, 2013, https://www.theguardian.com/science/2013/feb/22/watson-crick-dna-60th-anniversary-double-helix.

8. J. D. Watson and F. H. C. Crick, “Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid,” Nature 171, (1953):737–738, http://dosequis.colorado.edu/Courses/MethodsLogic/papers/WatsonCrick1953.pdf.

9. Brenda Maddox, “DNA’s double helix: 60 years since life’s deep molecular secret was discovered,” Guardian, February 22, 2013, https://www.theguardian.com/science/2013/feb/22/watson-crick-dna-60th-anniversary-double-helix.

10. Symposium held at Ohio Wesleyan University, Delaware, on April 6, 1963. The proceedings were published in The Control of Human Heredity and Evolution (1965).

11. S. E. Luria, The Control of Human Heredity and Evolution, ed. T. M. Sonneborn (New York: Macmillan, 1965).

12. E. M. Witkin, “Remembering Rollin Hotchkiss (1911–2004),” Genetics 170, (2005): 1443–1447, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1449782/.

13. R. Hotchkiss, The Control of Human Heredity and Evolution, ed. T. M. Sonneborn (New York: Macmillan, 1965).

14. R. Sinsheimer, “The End of the Beginning,” (lecture, Caltech, October 26, 1966). Excerpt in Human Nature (2019).

15. R. Sinsheimer, “The Prospect of Designed Genetic Change,” American Scientist XXXII, (1969): 8–13, http://calteches.library.caltech.edu/2718/1/genetic.pdf.

16. M. Nirenberg, “Will society be prepared?,” Science 157, (1967): 633, https://science.sciencemag.org/content/157/3789/633.

17. J. Lederberg, “Molecular biology, eugenics and euphenics,” Nature 198, (1963): 428–429, https://www.nature.com/articles/198428a0.pdf.

18. J. A. Wolff and J. Lederberg, “An early history of gene transfer and therapy,” Human Gene Therapy 5, (1994): 469–480, https://www.liebertpub.com/doi/abs/10.1089/hum.1994.5.4-469.

19. J. Lederberg, “DNA breakthrough points way to therapy by virus,” Washington Post, January 13, 1968, https://profiles.nlm.nih.gov/ps/access/BBABSP.pdf.

20. J. Lederberg, in J. A. Wolff and J. Lederberg, “An early history of gene transfer and therapy,” Human Gene Therapy 5, (1994): 469–480, https://www.liebertpub.com/doi/abs/10.1089/hum.1994.5.4-469.

21. N. A. Wivel and W. F. Anderson, “Human Gene Therapy: Public Policy and Regulatory Issues,” in The Development of Human Gene Therapy, ed. T. Friedmann (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1999), pp 671–689.

Chapter 10: The Rise and Fall of Gene Therapy

1. S. Rogers, “Shope papilloma virus: A passenger in man and its significance to the potential control of the host genome,” Nature 212, (1966): 1220–1222, https://www.nature.com/articles/2121220a0.

2. T. Friedmann and R. Roblin, “Gene therapy for human genetic disease?,” Science 175, (1972): 949–955, https://science.sciencemag.org/content/175/4025/949.long.

3. JapanPrize, “2015 Japan Prize Commemorative Lecture: Dr. Theodore Friedmann & Prof. Alan Fischer,” YouTube video, 1:07:56, last viewed June 7, 2020, https://www.youtube.com/watch?v=Z5SLxpPLxcw&t=136s.

4. David Baltimore, “Limiting science: A biologist’s perspective,” Daedalus, 107, (1978): 37–45, https://www.jstor.org/stable/20024543?seq=1.

5. M. J. Cline, “Perspectives for gene therapy: inserting new genetic information into mammalian cells by physical techniques and viral vectors,” Pharmacology & Therapeutics 29, (1985): 69–92.

6. P. Jacobs, “Doctor tried gene therapy on 2 humans,” Washington Post, October 8, 1980, https://www.washingtonpost.com/archive/politics/1980/10/08/doctor-tried-gene-therapy-on-2-humans/c95d4b44-3e5c-4a48-904c-4bbefe52391b/?utm_term=.b867c1010e22.

7. D. Bartels, “Gene therapy: scientific advances and socio-ethical considerations,” Journal of Social & Biological Structures 9, (1986) 105–113, https://psycnet.apa.org/record/1987-32279-001.

8. E. Beutler, “The Cline affair,” Molecular Therapy 4, (2001): 396–397. https://www.cell.com/action/showPdf?pii=S1525-0016%2801%2990486-1.

9. R. Williamson, “Gene therapy,” Nature 298, (1982): 416–418, https://www.nature.com/articles/298416a0.

10. W. F. Anderson, “Prospects for human gene therapy,” Science 226, (1984): 401–409, https://science.sciencemag.org/content/226/4673/401.long.

11. P. Gorner and J. Lyon, “Altered Fates,” Chicago Tribune, March 7, 1986, https://www.chicagotribune.com/news/ct-xpm-1986-03-07-8601170568-story.html.

12. Jonathan Gardner, “New estimate puts cost to develop a new drug at $1B, adding to long -running debate,” BioPharma Dive, March 3, 2020, https://www.biopharmadive.com/news/new-drug-cost-research-development-market-jama-study/573381/.

13. Larry Thompson, “Human gene therapy debuts at NIH,” Washington Post, September 15, 1990, https://www.washingtonpost.com/archive/politics/1990/09/15/human-gene-therapy-debuts-at-nih/f98ffb56-aa7f-4529-a5f6-c57cb845a7cd/?utm_term=.82d9fd43ca22.

14. Jeff Lyon and Peter Gomer, Altered Fates: Gene Therapy and the Retooling of Human Life (New York: W. W. Norton & Co., 1996).

15. Robin Marantz Henig, “Dr. Anderson’s gene machine,” New York Times, March 31, 1999, https://www.nytimes.com/1991/03/31/magazine/dr-anderson-s-gene-machine.html.

16. Peter Gorner, “Doctors begin world’s first gene therapy,” Chicago Tribune, September 15, 1990, http://articles.chicagotribune.com/1990-09-15/news/9003170543_1_dr-w-french -anderson-gene-therapy-adenosine-deaminase.

17. L. M. Muul et al., “Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial,” Blood 101, (2003): 2563–2569, https://pubmed.ncbi.nlm.nih.gov/12456496/.

18. J. M. Wilson, “Recollections from a Pioneer Who Provided the Foundation for the Success of Gene Therapy in Treating Severe Combined Immune Deficiencies,” Human Gene Therapy 27, (2016): 53–56, https://www.liebertpub.com/doi/10.1089/humc.2016.29013.int.

19. T. Friedmann, “A brief history of gene therapy,” Nature Genetics 2, (1992): 93–98, https://www.nature.com/articles/ng1092-93.

20. Natalie Angier, “Gene experiment to reverse inherited disease is working,” New York Times, April 1, 1994, https://www.nytimes.com/1994/04/01/us/gene-experiment-to-reverse-inherited-disease-is-working.html.

21. S. H. Orkin and A. G. Motulsky, “Report and recommendations of the panel to assess the NIH investment in research on gene therapy,” OSP, December 7, 1995, https://osp.od.nih.gov/wp-content/uploads/2014/11/Orkin_Motulsky_Report.pdf.

22. T. Friedmann, “Preface,” in The Development of Human Gene Therapy (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1999).

23. Paul Gelsinger, “Jesse’s Intent,” http://www.jesse-gelsinger.com/jesses-intent.html.

24. Rick Weiss and Deborah Nelson, “Teen dies undergoing experimental gene therapy,” Washington Post, September 29, 1999, https://www.washingtonpost.com/wp-srv/WPcap/1999-09/29/060r-092999-idx.html?noredirect=on.

25. Sheryl Gay Stolberg, “The biotech death of Jesse Gelsinger,” New York Times, November 28, 1999, https://www.nytimes.com/1999/11/28/magazine/the-biotech-death-of-jesse-gelsinger.html.

26. S. E. Raper et al., “Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adnoviral gene transfer,” Molecular Genetics and Metabolism 80, (2003): 148–158, https://pubmed.ncbi.nlm.nih.gov/14567964/.

27. Peter Little, Genetic Destinies (Oxford, UK: Oxford University Press, 2002).

28. Siddhartha Mukherjee, The Gene: An Intimate History (New York: Simon & Schuster, 2017).

29. The Gene, PBS 2020, https://www.pbs.org/show/gene/.

30. H. F. Judson, “The Glimmering Promise of Gene Therapy.” MIT Technology Review, November 1, 2006, https://www.technologyreview.com/s/406797/the-glimmering-promise-of-gene-therapy/.

31. Ibid.

32. K. Davies, “From the Cultural Revolution to the Gene Therapy Revolution: An Interview with Guangping Gao, PhD,” Human Gene Therapy, February 14, 2020, https://www.liebertpub.com/doi/abs/10.1089/hum.2020.29109.int.

33. Ryan Cross, “The redemption of James Wilson.” Chemical & Engineering News, September 2019, https://cen.acs.org/business/The-redemption-of-James-Wilson-gene-therapy-pioneer/97/i36.

34. David Schaffer, TRI-CON, San Francisco, March 2, 2019.

35. Julianna LeMieux, “Going Viral: The Next Generation of AAV Vectors,” Genetic Engineering & Biotechnology News, September 3, 2019, https://www.genengnews.com/insights/going-viral-the-next-generation-of-aav-vectors/.

36. Editorial, “Gene therapy deserves a fresh chance,” Nature 461, (2009): 1173, https://www.nature.com/articles/4611173a.

37. Melinda Wenner, “Gene therapy: An interview with an unfortunate pioneer,” Scientific American, September 1, 2009, https://www.scientificamerican.com/article/gene-therapy-an-interview/?redirect=1.

38. Carl Zimmer, “Gene therapy emerges from disgrace to be the next big thing, again,” WIRED, August 13, 2013, https://www.wired.com/2013/08/the-fall-and-rise-of-gene-therapy-2/.

39. JapanPrize, “2015 Japan Prize Commemorative Lecture: Dr. Theodore Friedmann & Prof. Alain Fischer,” YouTube video, 1:07:56, last viewed June 30, 2020, https://youtu.be/Z5SLxpPLxcwe.

Chapter 11: Overnight Success

1. Ricki Lewis, “Luxturna: A giant step forward for blindness gene therapy—a conversation with Dr. Kathy High,” DNA Science Blog, July 20, 2017, https://blogs.plos.org/dnascience/2017/07/20/luxturna-a-giant-step-forward-for-blindness-gene-therapy-a-conversation-with-dr-kathy-high/.

2. David Dobbs, “Why there’s new hope about ending blindness,” National Geographic, September 2016, https://www.nationalgeographic.com/magazine/2016/09/blindness-treatment-medical-science-cures/.

3. ASGCT, “Seeing the Light with Retinal Gene Therapy: From Fantasy to Reality—Jean Bennett,” YouTube video, 45:37, last viewed June 30, 2020, https://youtu.be/jDdFmBxNfUE.

4. J. M. Wilson, “Interview with Jean Bennett, MD, PhD,” Human Gene Therapy 29, (2018): 7–9, https://doi.org/10.1089/humc.2018.29032.int.

5. A. W. Taylor, “Ocular immune privilege,” Eye 23, (2009): 1885–1889, https://www.nature.com/articles/eye2008382.

6. Jean Bennett, “My Career Path for Developing Gene Therapy for Blinding Diseases: The Importance of Mentors, Collaborators, and Opportunities,” Human Gene Therapy 25, (2014): 663–670, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137328/.

7. J. M. Wilson, “Interview with Jean Bennett, MD, PhD,” Human Gene Therapy 29, (2018): 7–9, https://doi.org/10.1089/humc.2018.29032.int.

8. A. Maguire et al., “Safety and efficacy of gene transfer for Leber’s Congenital Amaurosis,” New England Journal of Medicine 358, (2008): 2240–2248, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829748/.

9. J. Bennett et al., “Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial,” Lancet 388, (2016): 661–672, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351775/.

10. Sharon Begley, “Out of prison, the ‘father of gene therapy’ faces a harsh reality: a tarnished legacy and an ankle monitor,” STAT, July 23, 2018, https://www.statnews.com/2018/07/23/w-french-anderson-father-of-gene-therapy/.

11. David Schaffer, TRI-CON conference, San Francisco, March 2, 2019.

12. S. Cannon, “Sickle cell disease advocate & precision medicine leader remembered,” Black Doctor, April 8, 2016, https://blackdoctor.org/my-story-any-day-without-pain-is-a-good-day/.

13. M. Friend, “Shakir Cannon, patient advocate,” CRISPR Journal 1, (2018): 24–25, https://www.liebertpub.com/doi/10.1089/crispr.2018.29005.mfr.

14. D. Shriner and C. N. Rotimi, “Whole-genome-sequence-based haplotypes reveal single origin of the sickle allele during the Holocene Wet Phase,” American Journal of Human Genetics 102, (2018): 547–556, https://www.cell.com/ajhg/fulltext/S0002-9297(18)30048-X.

15. T. L. Savitt and M. F. Goldberg, “Herrick’s 1910 case report of sickle cell anemia,” Journal of the American Medical Association 261, (1989): 266–271, https://doi.org/10.1001/jama.1989.03420020120042.

16. Editorial, “Sickle cell anemia, a race specific disease,” Journal of the American Medical Association 133, (1947): 33–34, https://jamanetwork.com/journals/jama/article-abstract/290758.

17. A. C. Allison, “Two lessons from the interface of genetics and medicine,” Genetics 166, (2004): 1591–1599, http://www.genetics.org/content/genetics/166/4/1591.full.pdf.

18. V. M. Ingram, “Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin,” Nature 180, (1957): 326–328, https://www.nature.com/articles/180326a0.

19. J. Lapook, “Could gene therapy cure sickle cell anemia?,” 60 Minutes, March 10, 2019, https://www.cbsnews.com/news/could-gene-therapy-cure-sickle-cell-anemia-60-minutes/.

20. J-A. Ribeil et al., “Gene therapy in a patient with sickle cell disease,” New England Journal of Medicine 376, (2017): 848–855, https://www.nejm.org/doi/full/10.1056/NEJMoa1609677.

21. J. Lapook, “Could gene therapy cure sickle cell anemia?,” 60 Minutes, March 10, 2019, https://www.cbsnews.com/news/could-gene-therapy-cure-sickle-cell-anemia-60-minutes/.

22. J. Watson, “Sickling in negro newborns: Its possible relationship to fetal hemoglobin,” American Journal of Medicine 5, (1948): 159–160, https://doi.org/10.1016/0002-9343(48)90029-1.

23. R. Daggy et al., “Health and disease in Saudi Arabia: The Aramco experience, 1940s–1990s,” University of California, 1998, http://texts.cdlib.org/view?docId=kt8m3nb5g6&doc.view=entire_text.

24. V. G. Sankaran et al., “Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A,” Science 322, (2008): 1839–1842, http://science.sciencemag.org/content/322/5909/1839.long.

25. K. Weintraub, “New gene therapy shows promise for patients with sickle cell disease,” WBUR, March 8, 2019, https://www.wbur.org/commonhealth/2019/03/08/gene-therapy-sickle-cell.

26. Sharon Begley, “NIH and Gates Foundation launch effort to bring genetic cures for HIV, sickle cell disease to world’s poor,” STAT, October 23, 2019, https://www.statnews.com/2019/10/23/nih-gates-foundation-genetic-cures-hiv-sickle-cell/.

27. Sean Nolan, “Unite to Cure,” The Vatican, April 26, 2018.

28. K. Foust et al., “Intravascular AAV9 preferentially targets neonatal-neurons and adult-astrocytes in CNS,” Nature Biotechnology 27, (2009): 59–65, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895694/.

29. J. R. Mendell et al., “Single-dose gene-replacement therapy for spinal muscular atrophy,” New Engl. J. Med. 377, (2017): 1713–1722, https://www.nejm.org/doi/full/10.1056/NEJMoa1706198.

30. Larry Luxner, “With Zolgensma’s approval, debate shifts to pricing and availability of world’s costliest drug,” SMA News Today, May 29, 2019, https://smanewstoday.com/2019/05/29/zolgensma-approval-shifts-debate-pricing-availability-worlds-costliest-drug/l.

31. Nathan Yates, “I have spinal muscular atrophy. Critics of the $2 million new gene therapy are missing the point,” STAT, May 31, 2019, https://www.statnews.com/2019/05/31/spinal-muscular-atrophy-zolgensma-price-critics/.

32. E. Mamcarz et al., “Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1,” New England Journal of Medicine 380, (2019); 1525–1534, https://www.nejm.org/doi/full/10.1056/NEJMoa1815408.

33. M. Cortez, “ ‘Bubble boys’ cured in medical breakthrough using gene therapy,” Bloomberg April 17, 2019, https://www.bloomberg.com/news/articles/2019-04-17/-bubble-boys-cured-in-medical-breakthrough-using-gene-therapy.

34. V. Montazerhodjat, D. M. Weinstock, and A. W. Lo, “Buying cures versus renting health: Financing health care with consumer loans,” Science Translational Medicine 8, (2016): 327, https://stm.sciencemag.org/content/8/327/327ps6.

35. George Church, interview, Boston, August 3, 2019.

36. Sarah Boseley, “Dismay at lottery for $2.1m drug to treat children with muscle-wasting disease,” Guardian, December 20, 2019, https://www.theguardian.com/society/2019/dec/20/lottery-prize-zolgensma-drug-zolgensma-children-muscle-wasting-disease.

37. F. W. Twort, “An investigation on the nature of ultra-microscopic viruses,” Lancet 186, (1915): 1241–1243.

38. A. Dublanchet, “The epic of phage therapy,” Canadian Journal of Infectious Diseases and Medical Microbiology 18, (2007): 15–18, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542892/.

39. Richard Martin, “How ravenous Soviet viruses will save the world,” WIRED, October 1, 2003, https://www.wired.com/2003/10/phages/.

40. M. Rosen, “Phage therapy treats patient with drug-resistant bacterial infection,” Howard Hughes Medical Institute, May 8, 2019, https://www.hhmi.org/news/phage-therapy-treats-patient-with-drug-resistant-bacterial-infection.

41. Julianna LeMieux, “Phage therapy win: Mycobacterium infection halted,” Genetic Engineering & Biotechnology News, May 8, 2019, https://www.genengnews.com/insights/phage-therapy-win-mycobacterium-infection-halted/.

42. Ben Fidler, “How an Ohio kids’ hospital quietly became ground zero for gene therapy,” Xconomy, April 15, 2019, https://xconomy.com/national/2019/04/15/how-an-ohio-kids-hospital-quietly-became-ground-zero-for-gene-therapy/.

43. Ryan Cross, “The redemption of James Wilson,” Chemical & Engineering News, September 2019, https://cen.acs.org/business/The-redemption-of-James-Wilson-gene-therapy-pioneer/97/i36.

44. Ibid.

45. C. Hinderer et al., “Severe Toxicity in Nonhuman Primates and Piglets Following High-Dose Intravenous Administration of an Adeno-Associated Virus Vector Expressing Human SMN,” Human Gene Therapy 29, (2018): 285–298.

46. Ben Fidler, “Two patients die in now-halted study of Audentes gene therapy,” BioPharma Dive, June 26, 2020, https://www.biopharmadive.com/news/audentes-gene-therapy-patient-deaths/580670/

47. Nicole Paulk, “Gene Therapy: It’s Time to Talk about High-Dose AAV,” Genetic Engineering & Biotechnology News, July 7, 2020, https://www.genengnews.com/topics/genome-editing/gene-therapy-its-time-to-talk-about-high-dose-aav/.

Chapter 12: Fix You

1. Rebecca Robbins, “Billionaire Sean Parker is nerding out on cancer research. Science has never seen anyone quite like him,” STAT, July 9, 2019, https://www.statnews.com/2019/07/09/sean-parker-cancer-research-science/.

2. F. Baylis and M. McLeod, “First-in-human Phase 1 CRISPR gene editing cancer trials: Are we ready?,” Current Gene Therapy 17, (2017): 309–319, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769084/.

3. Preetika Rana, Amy Dockser Marcus, and Wenxin Fan, “China, Unhampered by Rules, Races Ahead in Gene-Editing Trials,” Wall Street Journal, January 21, 2018, https://www.wsj.com/articles/china-unhampered-by-rules-races-ahead-in-gene-editing-trials-1516562360.

4. E. A. Stadtmauer et al., “CRISPR-engineered T cells in patients with refractory cancer,” Science 367, (2020): eaba7365, https://science.sciencemag.org/content/367/6481/eaba7365.

5. Carl June, Keystone Symposium, Banff, Canada, February 9, 2020.

6. G. E. Martyn et al., “Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding,” Nature Genetics 50, (2018): 498–503, https://www.nature.com/articles/s41588-018-0085-0.

7. M. H. Porteus, “A New Class of Medicines through DNA Editing,” New England Journal of Medicine 380, (2019): 947–959, https://www.nejm.org/doi/full/10.1056/NEJMra1800729.

8. Matthew Porteus, International Human Genome Editing Summit, Hong Kong, November 29, 2018.

9. David Sanchez in Human Nature (2019), https://wondercollaborative.org/human-nature-documentary-film/.

10. Rob Stein, “In a 1st, doctors In U.S. use CRISPR tool to treat patient with genetic disorder,” NPR, July 29, 2019, https://www.npr.org/sections/health-shots/2019/07/29/744826505/sickle-cell-patient-reveals-why-she-is-volunteering-for-landmark-gene-editing-st.

11. Rob Stein, “A Patient Hopes Gene-Editing Can Help With Pain Of Sickle Cell Disease,” NPR, October 10, 2019, https://www.npr.org/sections/health-shots/2019/10/10/766765780/after-a-life-of-painful-sickle-cell-disease-a-patient-hopes-gene-editing-can-hel.

12. Rob Stein, “A Young Mississippi Woman’s Journey Through a Pioneering Gene-Editing Experiment,” NPR, December 25, 2019, https://www.npr.org/sections/health-shots/2019/12/25/784395525/a-young-mississippi-womans-journey-through-a-pioneering-gene-editing-experiment.

13. Rob Stein, “A Year In, 1st Patient To Get Gene Editing For Sickle Cell Disease is Thriving,” NPR, June 23, 2020, https://www.npr.org/sections/health-shots/2020/06/23/877543610/a-year-in-1st-patient-to-get-gene-editing-for-sickle-cell-disease-is-thriving.

14. K. Davies and E. Charpentier, “Finding Her Niche: An Interview with Emmanuelle Charpentier,” CRISPR Journal 2, (2019): 17–22, https://doi.org/10.1089/crispr.2019.29042.kda.

15. Bill Gates, “Gene Editing for Good,” Foreign Affairs, May/June 2018, https://www.foreignaffairs.com/articles/2018-04-10/gene-editing-good.

16. Kevin Davies, “Avila Therapeutics Targets the Covalent Proteome,” Bio-IT World, January 28, 2010, http://www.bio-itworld.com/2010/01/28/avila.html.

17. M. L. Maeder et al., “Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10,” Nature Medicine 25, (2019): 229–233, https://www.nature.com/articles/s41591-018-0327-9.

18. Marilynn Marchione, “Doctors try 1st CRISPR editing in the body for blindness,” AP News, March 4, 2020, https://apnews.com/17fcd6ae57d39d06b72ca40fe7cee461.

19. Rob Wright, “A CEO’s most formative leadership experience,” Life Science Leader, February 25, 2019, https://www.lifescienceleader.com/doc/a-ceo-s-most-formative-leadership-experience-0001.

20. Rob Wright, “John Leonard’s latest adventure—readying Intellia Therapeutics for the long haul,” Life Science Leader, March 1, 2019, https://www.lifescienceleader.com/doc/john-leonard-s-latest-adventure-readying-intellia-therapeutics-for-the-long-haul-0001.

21. Alliance for Regenerative Medicine, “2017 Annual Dinner,” YouTube video, 1:10:07, last viewed May 2, 2020, https://www.youtube.com/watch?v=wPKyr092HlE.

22. Amy Dockser Marcus, “A year of brutal training for racing in the Andes,” Wall Street Journal, February 10, 2017, https://www.wsj.com/articles/a-year-of-brutal-training-for-racing-in-the-andes-1486814400.

23. Rodolphe Barrangou, interview, Victoria, Canada, February 21, 2019.

24. U. A. Neil, “A conversation with Eric Olson,” Journal of Clinical Investment 127, (2017): 403–404, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5272177/.

25. L. Amoasii et al., “Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy,” Science 362, (2018): 86–91, https://science.sciencemag.org/content/362/6410/86.

26. V. Iyer et al., “No unexpected CRIPR-Cas9 off-target activity revealed by trio sequencing of gene-edited mice,” PLOS Genetics, July 9, 2018, https://doi.org/10.1371/journal.pgen.1007503.

27. J. H. Hu et al., “Chemical Biology Approaches to Genome Editing: Understanding, Controlling and Delivering Programmable Nucleases,” Cell Chemical Biology 23, (2016): 57–73, https://doi.org/10.1016/j.chembio.2015.12.009.

28. M. Kosicki et al., “Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements,” Nature Biotechnology 36, (2018): 765–771, https://www.nature.com/articles/nbt.4192.

29. C. T. Charlesworth et al., “Identification of preexisting adaptive immunity to Cas9 proteins in humans,” Nature Medicine 25, (2019): 249–254, https://www.nature.com/articles/s41591-018-0326-x.

30. A. Mehta and O. M. Merkel, “Immunogenicity of Cas9 Protein,” Journal of Pharmaceutical Sciences 109, (2020): 62–67, https://pubmed.ncbi.nlm.nih.gov/31589876/.

31. T. Ho and D. P. Lane, “Guardian of Genome Editing,” CRISPR Journal 1, (2018): 258–260, https://www.liebertpub.com/doi/10.1089/crispr.2018.29021.dal.

Chapter 13: Patent Pending

1. Jennifer Doudna, “How CRISPR lets us edit our DNA,” TED, September 2015, https://www.ted.com/talks/jennifer_doudna_how_crispr_lets_us_edit_our_dna.

2. Jacob Sherkow, “How much is a CRISPR patent license worth?,” Forbes, February 21, 2017, https://www.forbes.com/sites/jacobsherkow/2017/02/21/how-much-is-a-crispr-patent-license-worth/#184e0a0d6b77.

3. M. Jínek, J. A. Doudna, E. Charpentier, and K. Chyliński, “Methods and Composition for RNA-directed site-specific DNA modification,” USPTO application, submitted May 25, 2012.

4. Jacob Sherkow, “The CRISPR patent landscape: Past, present, and future,” CRISPR Journal 1, (2018): 9–11, https://www.liebertpub.com/doi/abs/10.1089/crispr.2018.0044.

5. Erik Sontheimer, NIH grant application, January 2009. Personal communication.

6. Jon Cohen, “How the battle lines over CRISPR were drawn,” Science, February 15, 2017, https://www.sciencemag.org/news/2017/02/how-battle-lines-over-crispr-were-drawn.

7. “Broad Institute Priority Statement,” Exhibit A, May 2016, https://www.broadinstitute.org/files/news/pdfs/BroadPriorityStatement.pdf.

8. Broad Communications, “For journalists: Statement and background on the CRISPR patent process,” January 16, 2020, https://www.broadinstitute.org/crispr/journalists-statement-and-background-crispr-patent-process.

9. Ibid.

10. Joe Stanganelli, “Interference: A CRISPR Patent Dispute Roadmap,” Bio-IT World, January 9, 2017, http://www.bio-itworld.com/2017/1/9/interference-a-crispr-patent-dispute-roadmap.aspx.

11. Sarah Zhang, “An Outdated Law Will Decide the CRISPR Patent Dispute,” Atlantic, December 7, 2016, https://www.theatlantic.com/science/archive/2016/12/crispr-patent-hearing/509747/.

12. Dana Carroll, “A CRISPR Approach to Gene Targeting,” Molecular Therapy 20, (2012): 1658–1660, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437577/.

13. Lin Shuailiang, email to Doudna, February 28, 2015, https://s3.amazonaws.com/files.technologyreview.com/p/pub/docs/CRISPR-email.pdf.

14. Antonio Regalado, “Patent Office hands win in CRISPR battle to Broad Institute,” MIT Technology Review, February 16, 2017, https://www.technologyreview.com/s/603662/patent-office-hands-win-in-crispr-battle-to-broad-institute/.

15. K. Davies, “The Evolving Law of CRISPR: Interview with Professor Jacob Sherkow of New York Law School,” Biotechnology Law Report 37, (2018): 126–130, https://www.liebertpub.com/doi/10.1089/blr.2018.29068.kd.

16. Andrew Pollack, “Harvard and M.I.T. scientists win gene-editing patent fight,” New York Times, February 15, 2017, https://www.nytimes.com/2017/02/15/science/broad-institute-harvard-mit-gene-editing-patent.html.

17. Sharon Begley, “University of California appeals CRISPR patent setback,” STAT, April 13, 2017, https://www.statnews.com/2017/04/13/crispr-patent-uc-appeal/.

18. Chuck Stanley, “Berkeley Defends Bid to Overrule PTAB in CRISPR row,” Law360, April 30, 2018, https://www.law360.com/ip/articles/1038721.

19. Michael Barnes, “The CRISPR revolution,” Catalyst 9, (2014): 18–20, https://issuu.com/ucb-catalyst/docs/catalyst-sp14?e=8644787/8584210.

20. Jacob Sherkow, “The CRISPR-Cas9 Patent Appeal: Where Do We Go From Here?,” CRISPR Journal 1, (2018): 309–311, https://www.liebertpub.com/doi/abs/10.1089/crispr.2018.0044.

21. Richard Harris, “East Coast Scientists Win Patent Case Over Medical Research Technology,” NPR, September 10, 2018, https://www.npr.org/2018/09/10/646422497/east-coast-scientists-win-patent-case-over-medical-research-technology.

22. Sharon Begley, “University of California to be granted long-sought CRISPR patent, possibly reviving dispute with the Broad Institute,” STAT, February 8, 2019, https://www.statnews.com/2019/02/08/the-university-of-california-gets-its-key-crispr-patent/.

23. Sharon Begley, “Patent office reopens major CRISPR battle between Broad Institute and Univ. of California,” STAT, June 25, 2019, https://www.statnews.com/2019/06/25/crispr-patents-interference/.

24. H. T. Greely, “CRISPR, Patents, and Nobel Prizes,” Los Angeles Review of Books, August 23, 2017, https://lareviewofbooks.org/article/crispr-patents-and-nobel-prizes/#!.

25. Christie Rizk, “CRISPR Patent Fight Turns Ugly as UC Accuses Broad Researchers of Lying About Claims,” Genomeweb, August 1, 2019, https://www.genomeweb.com/business-news/crispr-patent-fight-turns-ugly-uc-accuses-broad-researchers-lying-about-claims#.Xvv3VkVKg2w.

26. Kerry Grens, “That Other CRISPR Patent Dispute,” The Scientist, August 31, 2016, https://www.the-scientist.com/daily-news/that-other-crispr-patent-dispute-32952.

27. Press release, “The Rockefeller University and Broad Institute of MIT and Harvard nnounce update to CRISPR-Cas9 portfolio filed by Broad,” Broad Institute, January 15, 2018, https://www.broadinstitute.org/news/rockefeller-university-and-broad-institute-mit-and-harvard-announce-update-crispr-cas9.

28. Jef Akst, “UC Berkeley receives CRISPR patent in Europe,” The Scientist, March 24, 2017, https://www.the-scientist.com/?articles.view/articleNo/48987/title/UC-Berkeley-Receives-CRISPR-Patent-in-Europe/.

29. Alex Philippidis, “Rejecting Broad Institute Opposition, EPO Affirms CRISPR Patent Issued to Charpentier, UC, and U. Vienna,” Genetic Engineering & Biotechnology News, February 10, 2020, https://www.genengnews.com/news/rejecting-broad-institute-opposition-epo-affirms-crispr-patent-issued-to-charpentier-uc-and-u-vienna/.

30. Hannah Kuchler, “Jennifer Doudna, CRISPR scientist, on the ethics of editing humans,” Financial Times, January 31, 2020, https://www.ft.com/content/6d063e48-4359-11ea-abea-0c7a29cd66fe.

31. Sharon Begley, “Fight for coveted CRISPR patents gets knottier, as MilliporeSigma makes new claims,” STAT Plus, July 22, 2019, https://www.statnews.com/2019/07/22/milliporesigma-crispr-patent-denial-challenge-university-california/.

32. Joe Stanganelli, “Interference: A CRISPR Patent Dispute Roadmap,” Bio-IT World, January 9, 2017, http://www.bio-itworld.com/2017/1/9/interference-a-crispr-patent-dispute-roadmap.aspx.

33. Jacob Sherkow, online interview, May 5, 2020.

Chapter 14: #CRISPRbabies

1. Marilynn Marchione, “AP Exclusive: US scientists try 1st gene editing in the body,” AP News, November 15, 2017, https://apnews.com/4ae98919b52e43d8a8960e0e260feb0a.

2. Aging Reversed, “AP—CRISPR babies in China,” YouTube video, 2:50, November 26, 2018, https://youtu.be/qUiNG1iW4Ww.

3. Jill Adams, “A conversation with Marilynn Marchione,” Open Notebook, June 25, 2019, https://www.theopennotebook.com/2019/06/25/storygram-marilynn-marchiones-chinese-researcher-claims-first-gene-edited-babies/#qanda.

4. Marilynn Marchione, email, July 25, 2019.

5. K. Musunuru, The Beagle Has Landed, December 7, 2018, https://beaglelanded.com/podcasts/kiran-musunuru/.

6. Antonio Regalado, Precision Medicine & Society Conference, Columbia University, April 24, 2019.

7. Hank Greely, TRI-CON, San Francisco, March 3, 2020.

8. M. Araki and T. Ishii, “International regulatory landscape and integration of corrective genome editing into in vitro fertilization,” Reproductive Biology and Endocrinology 12, (2014): 108, https://doi.org/10.1186/1477-7827-12-108.

9. Cody Sheehy, “A Unique Partnership: Code of the Wild,” CRISPR Journal 1, (2018): 135–136, https://www.liebertpub.com/doi/10.1089/crispr.2018.29009.csh.

10. Antonio Regalado, “Years before CRISPR babies, this man was the first to edit human embryos,” MIT Technology Review, December 11, 2018, https://www.technologyreview.com/s/612554/years-before-crispr-babies-this-man-was-the-first-to-edit-human-embryos/.

11. E. Lanphier et al., “Don’t Edit the Human Germline,” Nature, March 12, 2015, https://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111.

12. P. Liang et al., “CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes,” Protein & Cell 6, (2015): 363–372, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417674/.

13. Samira Kiani, phone interview, January 29, 2019.

14. He Jiankui, “Evaluation of the safety and efficacy of gene editing with human embryo CCR5 gene,” Chinese Clinical Trial registry, November 8, 2018 (withdrawn November 30, 2018), http://www.chictr.org.cn/showprojen.aspx?proj=32758.

15. Nie Jing-Bao, “He Jiankui’s genetic misadventure: Why him? Why China?,” Hastings Center, December 5, 2018, https://www.thehastingscenter.org/jiankuis-genetic-misadventure-china/. (Additional translation courtesy of Nicholas Shadid.)

16. Antonio Regalado, “Exclusive: Chinese scientists are creating CRISPR babies,” MIT Technology Review, November 25, 2018, https://www.technologyreview.com/s/612458/exclusive-chinese-scientists-are-creating-crispr-babies/.

17. Marilynn Marchione, “Chinese researcher claims first gene-edited babies,” Associated Press, November 26, 2018, https://www.apnews.com/4997bb7aa36c45449b488e19ac83e86d.

18. The He Lab, “About Lulu and Nana: Twin Girls Born Healthy After Gene Surgery As Single-Cell Embryos,” YouTube video, 4:43, last viewed June 30, 2020, https://www.youtube.com/watch?v=th0vnOmFltc.

19. Living MacTavish, “In Conversation With Scientist and CRISPR Pioneer Jennifer Doudna,” YouTube video, 47:30, November 30, 2017, https://www.youtube.com/watch?v=YVoPRSPEpvU&list=PLdT7Y4C6bsoSUdt2PB1NQlVQgKULTARXk&index=47&t=1898s.

20. Paul Knoepfler, TEDx Vienna, October 2015, https://www.ted.com/talks/paul_knoepfler_the_ethical_dilemma_of_designer_babies?language=en.

21. University of California Television, “Jennifer Doudna in Conversation with Joe Palca,” YouTube video, 58:54, last viewed June 30, 2020, https://youtu.be/0nMbNPb3CLc.

22. Pam Belluck, “How to stop rogue gene-editing of human embryos?,” New York Times, January 23, 2019, https://www.nytimes.com/2019/01/23/health/gene-editing-babies-crispr.html.

Chapter 15: The Boy from Xinhua

1. Yangyang Cheng, “Brave new world with Chinese characteristics,” Bulletin of the Atomic Scientists, December 21, 2018, https://thebulletin.org/2018/12/brave-new-world-with-chinese-characteristics/.

2. Zoe Low, “China’s gene editing Frankenstein He Jiankui, dubbed ‘mad genius’ by colleagues, had early dreams of becoming Chinese Einstein,” South China Morning Post, November 27, 2018, https://www.scmp.com/news/china/society/article/2175267/chinas-gene-editing-frankenstein-dubbed-mad-genius-colleagues-had.

3. Yangyang Cheng, “Brave new world with Chinese characteristics,” Bulletin of the Atomic Scientists, December 21, 2018, https://thebulletin.org/2018/12/brave-new-world-with-chinese-characteristics/.

4. J. He and M. W. Deem, “Heterogeneous diversity of spacers within CRISPR (clustered regularly interspaced short palindromic repeats),” Physical Review Letters 105, (2010): 128102, https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.105.128102#fulltext.

5. Kevin Davies, The $1,000 Genome (New York: Free Press, 2010).

6. Patrick Hoge, “Stephen Quake is ‘out to hunt death down and punch him in the face,’ ” San Francisco Business Times, June 8, 2017, https://www.bizjournals.com/sanfrancisco/news/2017/06/08/biotech-2017-stephen-quake-chan-zuckerberg-biohub.html.

7. D. Pushkarev et al., “Single-molecule sequencing of an individual human genome,” Nature Biotechnology 27, (2009): 847–850, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117198/.

8. Kevin Davies, “Quake Sequences Personal Genome Using Helicos Single-Molecule Sequencing,” Bio-IT World, August 10, 2019, http://www.bio-itworld.com/news/08/10/09/stephen-quake-personal-genome-single-molecule-sequencing.html.

9. E. A. Ashley et al., “Clinical evaluation incorporating a personal genome,” Lancet 375, (2010): 1525–1535, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937184/.

10. Kevin Davies, “The Medical Utility of Genome Sequencing,” Bio-IT World, June 8, 2011, http://www.bio-itworld.com/2011/issues/may-jun/medical-utility-genome-sequencing.html.

11. Steve Lombardi, phone interview, July 23, 2019.

12. H. C. Fan et al., “Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood,” Proceedings of the National Academy of Sciences 105, (2008): 16266 –16271, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562413/.

13. N. Jiang, J. He, J. A. Weinstein et al., “Lineage Structure of the Human Antibody Repertoire in Response to Influenza Vaccination,” Science Translational Medicine 5, (2013): 171ra19, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699344/.

14. Kevin Davies, “The bedrock of BGI: Huanming Yang,” Bio-IT World, September 27, 2011, http://www.bio-itworld.com/issues/2011/sept-oct/bedrock-bgi-huanming-yang.html.

15. Allison Proffitt, “Sequencing the human secret,” Bio-IT World, September 28, 2010, http://www.bio-itworld.com/2010/issues/sep-oct/bgi-hk.html.

16. R. Li et al., “The sequence and de novo assembly of the giant panda genome,” Nature 463, (2010): 311–317, https://www.nature.com/articles/nature08696.

17. Julianna LeMieux, “MGI Delivers the $100 Genome at AGBT,” Genetic Engineering & Biotechnology News, February 26, 2020, https://www.genengnews.com/topics/omics/mgi-delivers-the-100-genome-at-agbt-conference/.

18. Michael Specter, “The Gene Factory,” New Yorker, December 29, 2013, https://www.newyorker.com/magazine/2014/01/06/the-gene-factory.

19. Karen Zhang, “Before gene-editing controversy, Chinese scientist He Jiankui was rising star who received 41.5 million yuan in government grants,” South China Morning Post, December 3, 2018, https://www.scmp.com/news/hong-kong/health-environment/article/2176131/gene-editing-controversy-chinese-scientist-he?onboard=true.

20. Aaron Krol, “Direct Genomics’ new clinical sequencer revives a forgotten DNA technology,” Bio-IT World, October 29, 2015, http://www.bio-itworld.com/2015/10/29/direct-genomics-new-clinical-sequencer-revives-forgotten-dna-technology.html.

21. Ibid.

22. Ibid.

23. Steve Lombardi, phone interview, July 23, 2019.

24. Hannah Devlin, “Britain’s House of Lords approves conception of three-person babies,” Guardian, February 24, 2015, https://www.theguardian.com/politics/2015/feb/24/uk-house-of-lords-approves-conception-of-three-person-babies.

25. Jessica Hamzelou, “Exclusive: World’s first baby born with new ‘3 parent’ technique,” New Scientist, September 27, 2016, https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/.

26. Ariana Eunjung Cha, “This fertility doctor is pushing the boundaries of human reproduction, with little regulation,” Washington Post, May 14, 2018, https://www.washingtonpost.com/national/health-science/this-fertility-doctor-is-pushing-the-boundaries-of-human-reproduction-with-little-regulation/2018/05/11/ea9105dc-1831-11e8-8b08-027a6ccb38eb_story.html.

27. Megan Molteni, “A Controversial Fertility Treatment Gets Its First Big Test,” WIRED, January 28, 2019, https://www.wired.com/story/a-controversial-fertility-treatment-gets-its-first-big-test/.

28. Emily Mullin, “Despite Calls for a Moratorium, More ‘Three-Parent’ Babies Expected Soon,” One Zero, September 16, 2019, https://onezero.medium.com/despite-calls-for-a-moratorium-more-three-parent-babies-expected-soon-8a2464165423.

29. Ian Sample, “World’s first baby born from new procedure using DNA of three people,” Guardian, September 27, 2016, https://www.theguardian.com/science/2016/sep/27/worlds-first-baby-born-using-dna-from-three-parents.

30. Emily Mullin, “U.S. researcher says he’s ready to start four pregnancies with ‘three-parent’ embryos,” STAT, April 18, 2019, https://www.statnews.com/2019/04/18/new-york-researcher-ready-to-start-pregnancies-with-three-parent-embryos/.

31. Kang Ning, “The Village That AIDS Tore Apart,” Sixth Tone, May 31, 2016, http://www.sixthtone.com/news/897/village-aids-tore-apart.

32. Roger Gosden, “Robert Edwards (1925–2013),” Nature 497, (2013): 318, https://www.nature.com/articles/497318a.

33. R. G. Edwards et al., “Early stages of Fertilization in vitro of Human Oocytes Matured in vitro,” Nature 221, (1969): 632–635, https://www.nature.com/articles/221632a0.

34. R. G. Edwards and D. J. Sharpe, “Social Values and Research in Human Embryology,” Nature 231, (1971): 87–91, https://www.nature.com/articles/231087a0?proof=trueInJun.

35. K. Dow, “ ‘The men who made the breakthrough’: How the British press represented Patrick Steptoe and Robert Edwards in 1978,” Reproductive Biomedicine & Society Online 4, (2017): 59–67, https://www.sciencedirect.com/science/article/pii/S2405661817300199.

36. Nicole Karlis, “More than 8 million IVF infants have been born worldwide: report,” Salon, July 5, 2018, https://www.salon.com/2018/07/05/more-than-8-million-ivf-infants-born-worldwide-report/.

37. Gina Kolata, “Robert G. Edwards dies at 87; Changed rules of conception with first ‘test tube baby,’ ” New York Times, April 10, 2013, https://www.nytimes.com/2013/04/11/us/robert-g-edwards-nobel-winner-for-in-vitro-fertilization-dies-at-87.html.

38. J. Benjamin Hurlbut, “Imperatives of Governance,” Perspectives in Biology and Medicine 63, (2020): 177–194, https://muse.jhu.edu/article/748059/pdf.